The overall goals of this grant application are to develop innovative Phase I and Phase II trials of new and promising agents of therapeutic approaches for primary malignant CNS tumors, and to provide a carefully maintained database of clinical trial results. MDACC will be part of the National Central Nervous System Consortium (NCNSC) of five clinical centers with the Central Operation Office/Coordinating Center located at MDACC. Some of the hypotheses, based on our own research interest, that we will test, with respect to specific clinical therapies, are: a) Combination of biological and cytotoxid chemotherapeutic agents that show synergistic activity in cell culture may be active in patients with primary malignant brain tumors. b) Anti-angiogenesis agents will inhibit tumor growth and/or invasion by suppression of new tumor vessel formation. c) Replacement of tumor suppresser gene will modify the malignant phenotype of malignant brain tumors. d) Oncogene encoded proteins, growth factors, angiogenic factors and their receptors that are associated with brain tumors can be potential therapeutic targets for antisense approaches. Based on these hypotheses, our specific aims are to: 1) Treat cerebral gliomas at progression or recurrence with new agents and innovatinve combinations of biological and chemotherapeutic agents in the form of Phase I and Phase II clinical trials. 2) Collaborate with other member clinical centers within the consortium to develop gene therapy trials of viral vectors or antisense approaches transferring knowledge learned in the laboratory to the clinic. 3) Continue laboratory modeling of molecular approaches to replace mutated/deleted tumor suppresser genes as well as to regulate the expression of oncogene encoded protein, growth factor and growth factor receptor targets with the aim of bringing these approaches to clinical trials by the consortium. 4) Maintain a patient data base on all patients with brain tumors including relevant clinical and laboratory data using the Protocol Data Management System (PDMS) software available at the MDACC.